Randomized, multi-site, dose-escalation study of the safety and immunogenicity of four dosage levels of Intramuscular (IM) Norovirus Bivalent VLP Vaccine adjuvanted with monophosphoryl lipid A (MPL) and aluminum hydroxide (AlOH) compared to controls. Subjects will receive two doses, by intramuscular (IM) injection, 28 days apart.

The hypotheses for this study are:

The incidence of adverse events after vaccination with IM Norovirus Bivalent VLP Vaccine will be similar to the incidence of adverse events after other IM vaccines including CERVARIX® which contains MPL and AlOH.

Two doses of IM Norovirus Bivalent VLP Vaccine will be more immunogenic than one dose.

The post-vaccination serum antibody responses, the number of antibody secreting cells (ASC), including homing markers, and memory B-cell responses directed against norovirus antigens will be increased after IM Norovirus Bivalent VLP Vaccine compared to controls.

Safety as determined by the occurrence of local and systemic signs and symptoms [ Time Frame: seven days after vaccination for local signs and symptoms and 28 days post each dose for other adverse events. One year followup after last dose for SAEs and significant new medical conditions. ] [ Designated as safety issue: Yes ]

Safety as determined by the occurrence of local and systemic signs and symptoms within seven days after vaccination as self reported by subjects via memory aid (Days 0 through 7 post each dose) and incidence of abnormal hematology and serum chemistry laboratory values. Safety will also be assessed by occurrence of Serious Adverse Events (SAEs) and onset of any significant new medical conditions for 365 days following the last study vaccination.

Cohort B: 50-64 years IM Norovirus Bivalent VLP Vaccine at the chosen dose from Cohort A

Cohort C: 65-85 years IM Norvirus Bivalent VLP Vaccine at the chosen dosage from Cohort A

Cohort D: 18-49 Years of Age IM Norovirus Bivalent VLP Vaccine at the Chosen Dosage from Cohort A

Placebo Comparator: Saline

Biological: Saline

Two doses 28 days apart

Eligibility

Ages Eligible for Study:

18 Years to 85 Years (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Subjects must meet all of the inclusion criteria listed below:

Signed written informed consent.

Age:

Cohort A: 18-49 years, inclusive

Cohort B: 50-64 years, inclusive

Cohort C: 65-85 years, inclusive

Health Status:

Cohort A: In good health as determined by a screening evaluation that includes vital signs, medical history, and physical exam within 45 days before administration of IM Norovirus Bivalent VLP Vaccine or control.

Cohorts B and C: In good health as determined by a screening evaluation that includes vital signs, medical history, and physical exam within 45 days before administration of IM Norovirus Bivalent VLP Vaccine or control. Any existing medical diagnoses or conditions must be stable based on medical history and targeted physical examination. A stable medical condition is defined as: (A) Clinically acceptable health outcomes for the specific condition over the prior 6 months and (B) No change in prescription medication(s), dose, or frequency over the prior 3 months. Acceptable changes in medications are: a change of health care provider or insurance company or that is made for financial reasons as long as the medications are in the same class and/or a change due to improvement in a disease outcome.

Expressed interest and availability to fulfill the study requirements

Female subjects must be of non-childbearing potential (surgically sterile or post-menopausal for ≥ 12 months), or if of childbearing potential (as determined by the investigator) must be practicing abstinence or using an effective licensed method of birth control (e.g. oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream, or foam; intrauterine contraceptive device, or Depo-Provera; skin patch; vaginal ring or cervical cap) for 30 days prior to vaccination and must agree to continue such precautions for at least 60 days after the last vaccination. A woman is eligible if she is monogamous with a male who has had a vasectomy. Male subjects must agree not to father a child for at least 60 days after the last vaccination and to practice abstinence or use an effective method of birth control as noted above.

Agrees not to participate in another clinical trial with an investigational product for the entire duration of the study one year after the last study dose i.e. 393 days.

Agrees to storage of unused clinical specimens for an indefinite period of time for future norovirus research or research on other gastrointestinal pathogens.

Exclusion Criteria:

Subjects who meet any of the exclusion criteria at baseline will be excluded from study participation. The exclusion criteria are:

History of any of the following medical illnesses:

Diabetes

Cancer

Heart disease (hospitalization for a heart attack, arrhythmia, or syncope)

Unconsciousness (other than a single brief "concussion")

Seizures (other than febrile seizures as a child <5 years old)

Recurrent infections (more than 3 hospitalizations for invasive bacterial infections such as pneumonia or meningitis)

Neuroinflamatory or auto-immune disease

Any current illness requiring daily medication other than the following:

Cohort A: Vitamins, birth control, anti-hypertensive medication, antihistamines or anti-depressant medication. The PI should consult with the Central Safety Monitor and/or the sponsor for any clarification of medications allowable.

Cohorts B and C: Vitamins, birth control, anti-hypertensive medication, antihistamines or anti-depressant medication or any current illness requiring daily medication other than as noted above in inclusion # 3. The PI should consult with the Central Safety Monitor and/or the sponsor for any clarification of medications allowable.

Allergies or hypersensitivity to any component of the vaccine including MPL and AlOH adjuvants.

For women of child bearing potential, positive serum pregnancy test within 14 days and urine pregnancy test within 24 hours of administering either dose of IM Norovirus Bivalent VLP Vaccine or control.

Nursing mother.

Temperature > 100.4oF or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within 3 days of administration of IM Norovirus Bivalent VLP Vaccine or control.

Previous participation in a Norovirus vaccine or challenge study.

Study site personnel or their family members.

Significant history of psychiatric hospitalization, alcohol abuse, or illicit drug use in the prior 5 years.

Completion of an investigational vaccine or drug study within 28 days before administration of IM Norovirus Bivalent VLP Vaccine or control.

Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.

Other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a subject participating in the trial, would render the subject unable to comply with the protocol or would interfere with the evaluation of the vaccine.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01168401